Search results for "linkage disequilibrium"

2018

Genome-Wide-Association-Studies have become a powerful method to link point mutations (e.g. single nucleotide polymorphisms (SNPs)) to a certain phenotype or a disease. However, their power to detect SNPs associated to polygenic diseases such as Alzheimer's Disease (AD) is limited, since they can only infer the pairwise relation of single SNPs to the phenotype and ignore possible effects of various SNP combinations. The common method to probe these possible complex genetic patterns is to compute a measure called linkage disequilibrium (LD). Despite the fact that several predictive patterns found with LD could successfully be applied to medical diagnosis, this measure still holds several dra…

Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes

2012

One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1…

Preselection statistics and Random Forest classification identify population informative single nucleotide polymorphisms in cosmopolitan and autochth…

2018

Commercial single nucleotide polymorphism (SNP) arrays have been recently developed for several species and can be used to identify informative markers to differentiate breeds or populations for several downstream applications. To identify the most discriminating genetic markers among thousands of genotyped SNPs, a few statistical approaches have been proposed. In this work, we compared several methods of SNPs preselection (Delta, F st and principal component analyses (PCA)) in addition to Random Forest classifications to analyse SNP data from six dairy cattle breeds, including cosmopolitan (Holstein, Brown and Simmental) and autochthonous Italian breeds raised in two different regions and …

Population differences in the International Multi-Centre ADHD Gene Project.

2008

Contains fulltext : 71443.pdf (Publisher’s version ) (Closed access) The International Multi-Centre ADHD Gene sample consists of 674 families from eight countries (Belgium, England, Germany, Holland, Ireland, Israel, Spain, and Switzerland) ascertained from clinics for combined-type attention definity hyperactivity disorder in an offspring. 863 SNPs were successfully genotyped across 47 autosomal genes implicated in psychiatric disorders yielding a single nucleotide polymorphism (SNP) density of approximately one SNP per 2.5 kb. A global test of heterogeneity showed 269 SNPs nominally significant (expected 43). Inclusion of the Israeli population accounted for approximately 70% of these nom…

Corrigendum to “Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans” [J. Neuroim…

2007

Allelic age of the USH2A c.2299delG mutation

2010

24 p., figuras y bibliografía

Tumor necrosis factor alpha promoter polymorphism at position -238 is associated with chronic active hepatitis C infection

1998

Tumor necrosis factor alpha (TNF-alpha) is involved in the pathogenesis of chronic hepatitis C virus infection. The gene for TNF-alpha is encoded in the major histocompatibility locus (MHC). Two polymorphisms at positions -308 and -238 in the TNF-alpha promoter region might influence TNF-alpha expression. These promoter polymorphisms have been linked previously to a number of infectious diseases. TNF-alpha promoter polymorphisms at positions -238 and -308 were studied by DNA sequencing and sequence-specific oligonucleotide hybridization in 82 individuals with chronic hepatitis C and 99 control subjects. Subjects had been HLA class I and class II typed in a previous study. The frequency of t…

Accounting for haplotype phase uncertainty in linkage disequilibrium estimation

2007

The characterization of linkage disequilibrium (LD) is applied in a variety of studies including the identification of molecular determinants of the local recombination rate, the migration and population history of populations, and the role of positive selection in adaptation. LD suffers from the phase uncertainty of the haplotypes used in its calculation, which reflects limitations of the algorithms used for haplotype estimation. We introduce a LD calculation method, which deals with phase uncertainty by weighting all possible haplotype pairs according to their estimated probabilities as evaluated by PHASE. In contrast to the expectation-maximization (EM) algorithm as implemented in the HA…

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

2013

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10…

Comparing RADseq and microsatellites for estimating genetic diversity and relatedness : Implications for brown trout conservation

2019

The conservation and management of endangered species requires information on their genetic diversity, relatedness and population structure. The main genetic markers applied for these questions are microsatellites and single nucleotide polymorphisms (SNPs), the latter of which remain the more resource demanding approach in most cases. Here, we compare the performance of two approaches, SNPs obtained by restriction-site-associated DNA sequencing (RADseq) and 16 DNA microsatellite loci, for estimating genetic diversity, relatedness and genetic differentiation of three, small, geographically close wild brown trout (Salmo trutta) populations and a regionally used hatchery strain. The genetic di…